Kaposi’s sarcoma-associated herpesvirus ORF17 plays a key role in capsid maturation.
Kaposi’s sarcoma-associated herpesvirus ORF17 plays a key role in capsid maturation.
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卡波西肉瘤相关疱疹病毒 ORF17 在衣壳成熟中发挥关键作用。
DOI：
10.1016/j.virol.2021.02.009
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Fujimuro M
中科院分区：
文献类型：
--
作者：
Tsurumi S;Watanabe T;Iwaisako Y;Suzuki Y;Nakano T;Fujimuro M
卡波西肉瘤相关疱疹病毒是伽马疱疹病毒亚家族的一种人类横纹病毒。虽然疱疹病毒是衣壳形成及其过程的良好研究模型，但KSHV的模型仍不清楚。编码病毒蛋白酶前体(ORF17-prePR)的KSHV ORF17被认为有助于衣壳的形成；然而，功能信息在很大程度上是未知的。在这里，我们通过产生ORF17缺失和ORF17蛋白酶死亡的KSHV来评估ORF17在衣壳形成中的作用。这两个突变体都显示出病毒产量的减少，但没有DNA复制。ORF17-R-mut在限制或释放部位(R-位)发生点突变，可将ORF17-prePR功能性地切割成一个蛋白水解酶(ORF17-PR)和一个装配区(ORF17-Pap/-AP)，但不能在病毒生产中发挥作用。此外，野生型KSHV产生了成熟的衣壳，而ORF17缺失和蛋白酶死亡的KSHV产生了B-衣壳(即具有圆形内部结构的闭合体)。因此，ORF17及其蛋白水解酶功能是衣壳成熟所必需的。
Kaposi's sarcoma-associated herpesvirus is a human rhadinovirus of the gammaherpesvirus sub-family. Although herpesviruses are well-studied models of capsid formation and its processes, those of KSHV remain unknown. KSHV ORF17 encoding the viral protease precursor (ORF17-prePR) is thought to contribute to capsid formation; however, functional information is largely unknown. Here, we evaluated the role of ORF17 during capsid formation by generating ORF17-deficient and ORF17 protease-dead KSHV. Both mutants showed a decrease in viral production but not DNA replication. ORF17 R-mut, with a point-mutation at the restriction or release site (R-site) by which ORF17-prePR can be functionally cleaved into a protease (ORF17-PR) and an assembly region (ORF17-pAP/-AP), failed to play a role in viral production. Furthermore, wild type KSHV produced a mature capsid, whereas ORF17-deficient and protease-dead KSHV produced a B-capsid, (i.e., a closed body possessing a circular inner structure). Therefore, ORF17 and its protease function are essential for appropriate capsid maturation.